The objective of this grant was to investigate the pathopoiesis of multiple sclerosis (MS) by conducting five studies using two populations of MS patients, one in a high pevalence area and one in a lower prevalence area. These studies include a cohort study of the natural history of MS in the two areas; an immunologic study of changes in immune status, clinical course and environmental exposures; a genetic study of families with multiple cases of MS; and a case-control study of patients and susceptibility matched siblings. Studies completed to date have suggested the existece of a multiple sclerosis susceptibility gene located on the sixth chromosome and a relationship between haplotype and mean measles titers in MS patients and their normal siblings. Data from the immunologic study suggest that patients have higher mean antibody titers and impaired cell-mediated immunity to measles. The relationship of immune differences to changes in clinical status and the relationship between immune responses and genetic types will be further studied; the rate of progression to disability, mortality and other factors will be compared between the two cohorts; and analysis of the case-control study will determine factors which are assciated with disease.